Oxybutynin or venlafaxine for hot flushes in women who cannot or prefer not to use hormone replacement therapy

Plain English Summary

Background and study aims
Most menopausal women experience vasomotor symptoms (VMS), including hot flushes and night sweats, lasting several years. They can have a significant impact on the lives of affected women. Hot flushes can be particularly severe for women taking endocrine therapies for treatment of breast cancer. Hormone replacement therapy (HRT) is the most effective treatment for hot flushes. However, some women are unable to take HRT because of other health conditions, such as a history of breast cancer. Others may choose not to take HRT because of concerns about the potential harms of HRT. All non-hormonal drugs are less effective than HRT and have side-effects.
The most commonly prescribed non hormonal treatment for menopausal hot flushes is called venlafaxine. There is evidence that oxybutynin, a medicine currently used to treat an overactive bladder, is effective in reducing the frequency of hot flushes and could be more effective than venlafaxine. We want to find out which of venlafaxine or oxybutynin is best for the relief of menopausal hot flushes.

Who can participate?
We will recruit 480 participants who are experiencing menopausal VMS symptoms but are unable to take HRT and 480 participants who prefer not to take HRT.

What does the study involve?
Participants will be randomly allocated to either oxybutynin or venlafaxine, and asked to take this treatment for 12 months. Participants will also be asked to keep a diary about their hot flushes and complete questionnaires at various points throughout the trial.

What are the possible benefits and risks of participating?
Benefits:
Not provided at time of registration
Risks:
Risk of inconvenience: Participants recruited in the hospital setting, may be required to stay in clinic a little longer than usual due to their participation in the trial when they first join. Trial processes have been simplified as much as possible to ensure participants can complete most of the trial data electronically. Where hospital trusts do not post trial treatments, then participants will be expected to collect their treatment.
Risk of harm: NICE guidelines recommend venlafaxine for menopausal symptoms in women with breast cancer. Oxybutynin is not licenced for menopausal symptoms. However, both medications have marketing authorisation for use for other conditions and have been used in other clinical trials for menopausal symptoms, their side effects are known and well documented. Adverse event data will be collected regularly during the trial (week 4,8,12,6, and 12 months). Adverse events will be patient reported via a questionnaire. At the week 12 follow up appointment, the research team will ask about adverse events, if patients have not completed questionnaire data. If an SAE is reported, the NCTU will be made aware (within 24 hours of the participant disclosing an SAE via a questionnaire or to the research team). The NCTU and the recruiting site may be asked to contact the participant to obtain further information to determine whether an event has occurred that fulfils the SAE criteria. The seriousness and causality will be reviewed independently by a medical monitor (the Chief Investigator) responsible for determining causality assessments.
Consent training: this will be provided to site research teams, so that they can ensure randomised women are prepared to accept either allocation, understand the titration schedule and the need to balance benefit against side effects. The research clinicians at sites and their research support staff will be contactable for participants throughout the trial, should they experience any symptoms or side effects. Participants will be supplied with a trial treatment leaflet, which will explain the dose escalation schedule.
The inclusion/exclusion criteria ensures that only those who cannot or do not want to use HRT will be included in the trial. The trial will not be conveyed as an alternative equivalent to HRT.
Risk of breach of confidentiality: All members of the research team will have undergone GCP training. No personal information will be sent to the research team prior to receiving a ‘consent to contact’ form from the potential participant. The REDCap database is designed so only relevant members of the research team can see outcome measures of their participants. It is a validated secure web-based platform which allows for data tracking via date stamped audit logs. REDCap meets GCP standards.
Pregnancy: women experiencing the menopause/perimenopause may become pregnant. To note those in the ‘prefer not to use HRT group’ will need to be over 45 years of age to be eligible. PPI feedback suggests that requesting perimenopausal women to use highly effective contraception may be a barrier to recruitment. Also, many of the highly effective methods are hormonal, which they do not wish to use or cannot. PPI feedback also suggested that asking about contraception could be problematic for some women, especially those from faith groups, who may not want to use or consider contraception. PPI felt that women would prefer the research team to be up front about the medication and the associated risks. They can cope with transparency and want to make informed decisions.
According to the BUMPS website (https://www.medicinesinpregnancy.org/Medicine--pregnancy/Venlafaxine/) most studies of pregnant women taking venlafaxine do not raise concern that it causes birth defects, stillbirth, preterm delivery, or low infant birth weight. However, for some pregnancy outcomes, only small numbers of women have been studied and ongoing research is ideally required. Similarly, with Oxybutynin (https://www.medicinesinpregnancy.org/Medicine--pregnancy/Oxybutynin/) there is limited research on its use during pregnancy, but there was no indication of any increased risk of miscarriage or birth defects in the babies.
Given what is known about the risks of the trial treatments, PPI feedback and the numbers of women who may become pregnant during trial participation, we would put the following measures in place.
-Women who are pregnant, thinking of becoming pregnant in the next 12 months, or breastfeeding will be excluded from the trial. This is an eligibility exclusion criterion.
-The PIS will inform women about the risks of pregnancy while taking trial treatment and will recommend the use of contraception, but it will not be compulsory. It will also explain that trial treatment would be stopped immediately if they become pregnant.
-Clinicians and site staff will be trained to discuss the risks associated with pregnancy prior to trial entry.

Where is the study run from?
University College London (UK)

When is the study starting and how long is it expected to run for?
May 2023 to August 2027

Who is funding the study?
National Institute for Health and Care Research (NIHR) (UK).

Who is the main contact?
Dr Melanie Davies, melanie.davies@ucl.ac.uk

Contact information

Study information

Eligibility

Locations

Countries of recruitment

• England
• Northern Ireland
• Scotland
• United Kingdom
• Wales

Study participating centre

Sponsor information

Funders

Funder type

Government

Results and Publications

Editorial Notes

27/09/2024: The public contact was updated.
25/09/2024: Recruitment was paused due to the unavailability of one of the test medications and the recruitment start date was changed from 30/09/2024 to 30/04/2025.
03/07/2024. The recruitment start date was changed from 30/07/2024 to 30/09/2024.
08/04/2024: The following changes were made to the trial record:
1. The recruitment start date was changed from 30/04/2024 to 30/07/2024.
2. The ethics approval was added.
05/01/2024: The recruitment start date was changed from 31/07/2023 to 30/04/2024.
01/12/2023: Internal review.
26/05/2023: Trial's existence confirmed by NHS HRA.